Gianfranco Lenti

Influence of Physical Training on Blood Glucose Control, Glucose Tolerance, Insulin Secretion, and Insulin Action in Non-insulin-dependent Diabetic Patients

This study has been designed to investigate, in five non-insulin-dependent diabetic patients, the influence of physical training (1 h a day, 7 days a wk for 6 wk, at 50–60% maximum oxygen uptake) on blood glucose control, glucose tolerance, insulin secretion, and insulin action. Physical training resulted in a significant improvement in blood glucose control, glucose tolerance, and insulin action. These results suggest that short-term intense physical training ameliorates the main metabolic derangements of non-insulin-dependent diabetes mellitus.

Insulin resistance in the aged: The role of the peripheral insulin receptors

In the healthy subject, glucose tolerance tends to decrease with age due to impaired insulin secretion and/or decreased peripheral insulin activity. An oral glucose (100 g) tolerance test was performed on 12 aged (70 +/- 4 yr) and 8 young (32 +/- 7 yr) subjects; these subjects underwent laparatomy for cholecystectomy or the management of abdominal diseases. Subcutaneous adipose tissue was removed during surgery and fat cells, prepared according to a personal modification of Rodbells method, were incubated in a medium containing monoiodo- and cold insulin to evaluate insulin binding and affinity constants. The results of the tolerance test pointed to an insulin resistant state i.e., impaired glucose tolerance coupled with normal plasma insulin, as previously shown also by us using other methods in the aged subject. The binding study demonstrates a distinct insulin receptor decrease in fat cells from the older subjects (185,000 +/- 19,200 as opposed to 310,000 +/- 12,000), without any change in affinity constants. The result indicates that insulin resistance in the aged may be attributed at least in part to a reduction in the number of insulin receptors on the target cells. This could be a consequence of aging itself, as proposed by other workers in the case of old fat rats.

Ganglioside treatment in diabetic peripheral neuropathy: A multicenter trial

SummaryGanglioside treatment was evaluated with a multicenter, randomized, double-blind, controlled, cross-overvs placebo trial in 140 insulin-treated diabetic subjects with peripheral neuropathy. The patients entered the study when they showed an impairment in at least two of the electroneurographic parameters, and were assigned to two protocols according to the presence and severity of their neurological symptoms. Ninety-seven diabetic subjects with no or mild symptoms were assigned to protocol I, whereas 43 symptomatic patients were assigned to protocol II. The treatment periods lasted 6 weeks with an intermediate washout period of 4 weeks. The treatment consisted in the daily i.m. administration of 20 mg gangliosides or of placebo. Electroneurographic parameters were recorded at the beginning and at the end of each treatment period, whereas clinical and metabolic data (mean daily plasma glucose, glycosuria and glycosylated hemoglobin) were evaluated every three weeks in protocol I and every two weeks in protocol II. No change in the metabolic parameters was observed throughout the trial period. However, the treatment induced a statistically significant improvement of paresthesias (protocol II) and of some electrophysiological parameters; in particular, ganglioside treatment improved MCV of peroneal nerve (p<0.03) in patients of protocol I, MCV of ulnar nerve (p<0.002) and SCV of median nerve (p<0.06) in patients of protocol II. Furthermore, 22 subjects of protocol II showed a ‘drug preference’ while 10 preferred placebo and 9 had no preference. In conclusion, ganglioside treatment seems to have a positive effect on diabetic peripheral neuropathy, improving both some symptoms and some electrophysiological parameters.

Genetic, Immunologic, and Environmental Heterogeneity of IDDM: Incidence and 12-Mo Follow-Up of an Italian Population

The 1-yr incidence of insulin-dependent diabetes mellitus (IDDM) in a population of the Piedmont and Aosta Valley area of Italy was recorded. Anti-virus antibodies (e.g., Coxsackie B1-6, mumps, cytomegalovirus), islet cell antibodies (ICAs), and H LA-A, -B, -C, and -DR were determined in 74 IDDM patients (38 males, 36 females) and in controls. Total IDDM incidence was 5.0/100,000, and the incidence for those <20 yr of age was 11.6/100,000. Anti-virus antibody frequency was not different in IDDM patients and controls. ICAs were present in 58% of IDDM patients at onset and in 30% after 12 mo, and complement-fixing ICAs were found in 39 and 17%, respectively. IDDM was significantly and positively associated with DR3/DR4 and negatively associated with DR2 and DR5. ICA frequency was significantly higher in DR3/DR4 heterozygote patients than in patients without DR3 and DR4. These results suggest that in this IDDM population 1) viral etiology is not evident, 2) ICAs offer only a partial pathogenetic explanation, and 3) genetic and immunologic heterogeneity is evident.

Continuous Subcutaneous Insulin Infusion and Postprandial Exercise in Tightly Controlled Type I (Insulin-Dependent) Diabetic Patients

The aim of this study was to investigate the influence of short-term submaximal postprandial exercise on plasma glucose concentrations in tightly controlled insulin-dependent diabetic patients treated by means of continuous subcutaneous insulin infusion (CSII). Two hours after breakfast, five diabetic patients and five healthy control subjects followed this protocol: 30 min of mild exercise, 30 min rest, 30 min of moderate exercise, 150 min rest. Serial determinations of plasma glucose, free insulin, and growth hormone (GH) were made. Similar control studies without exercise were also performed. In the diabetic patients, analysis of variance and covariance did not reveal any significant difference between the 2-h postbreakfast concentrations of plasma glucose and free insulin and postexercise values. A significant GH increase was observed after the exercise periods. Plasma glucose and insulin concentrations throughout the exercise study were not significantly different from the control study concentrations. Plasma free insulin concentrations of the diabetic patients were higher than the concentrations of healthy subjects. We conclude that CSII-treated, tightly controlled, insulin-dependent diabetic patients performing short-term mild and moderate exercises 2 and 3 h after breakfast do not have a high risk of hypoglycemia in spite of mild hyperinsulinemia.

Rapid changes of glycosylated hemoglobin in diabetics submitted to artificial pancreas control

This study was performed in order to investigate the possibility of rapid changes in glycosylated hemoglobin levels. Hb A1(a+b+c) values were evaluated by a chromatographic Column Test (Bio-Rad) in 20 insulin-dependent diabetic patients before and after 48 h of glycemic control obtained by an artificial pancreas (Biostator Miles). A significant decrease of glycosylated hemoglobin levels was observed: from 11.21±2.8% to 9.89±2.15% of total hemoglobin content (p < 0.005). Our data bring to the conclusion that rapid changes of glycosylated hemoglobin partially reduce, but do not abolish the clinical significance of Hb A, determination as a reliable index of long-term glycemic control in diabetic patients.

Insulin receptors in adipocytes of non-diabetic and diabetic subjects. Preliminary report

SummaryWe have measured insulin binding to human adipocytes isolated from subcutaneous adipose tissue removed during surgery in normal and insulin-independent diabetics. Collagenase digestion,125I-monoiodoinsulin and Scatchard’s plot were employed to analyze the results. Different kinetic patterns emerged together with differences in the dissociation constant and receptor numbers: in normal subjects K1 was 4 × 10−9 moles/l and K2 0.5 × 10−8 moles/l, and in diabetic subjects K1 was 2.24 × 10−9 moles/l and K2 0.52 × 10−8 moles/l; the two classes of receptors were 100,000 and 300,000 per cell in normals and 50,000 and 180,000 in diabetics. It was clear that even slight diabetes leads to receptor deficiency in adipocytes, though it could not be determined whether this a primary, perhaps genetic, defect or secondary to antibody damage, as suggested by some workers. Feed-back between circulating insulin and specific receptor availability in cells is another possibility.

The treatment of unstable type I diabetes: Conventional versus portable pump insulin administration

SummaryThe treatment of unstable insulin-dependent diabetics (UIDD) is still an unsolved problem. A comparison was made between optimized conventional treatment (OCT) (Ultralente® + Actrapid® at breakfast, Actrapid® at lunch and Actrapid® at dinner) and continuous s.c. insulin infusion (CSII) for 30 days in 10 UIDD outpatients. Continuous 24-h blood glucose monitoring with an artificial pancreas, fasting values of HbA1, plasma lipids, growth hormone, glucagon, daily urinary glucose and protein excretion were recorded after each treatment; a daily blood glucose profile was determined every week. Daily mean blood glucose values dropped significantly (p<0.001): from 187.2 ± 66.6 (OCT) to 111.6 ± 27.0 mg/dl (CSII), and hypoglycemic and ketotic events disappeared during CSII. A significant improvement (p<0.01 − p<0.001) in all other parameters was also observed. It is suggested that CSII may help to improve metabolic control and the quality of life in UIDD.

Effect of a somatostatin analog on insulin requirement and hormone levels in 6 insulin-dependent juvenile-onset diabetics subjected to artificial pancreas

SummaryThis study was performed in order to investigate the effect of a 12-h infusion of the somatostatin selective analog D-Trp3, D-Cys14 Serono, (SRIF-A), on insulin requirement and C-peptide (CP), growth hormone (GH) and glucagon (IRG) levels in 6 insulin-dependent diabetics submitted to 60-h artificial pancreas (Biostator Miles) metabolic control from 2000 of the first day to 0800 of the fourth day. Meals were given at 1200 and 1700 of the second and third day. Before meals and 1–2 h after meals, plasma levels of CP, GH and IRG were measured. The two 12-h periods (midday-midnight) with and without continuous SRIF-A 12-h infusion (40 µg/h) were considered. The SRIF-A infusion caused a 20% reduction in insulin requirement (p<0.05) and a slight but significant reduction of GH levels (p<0.05). CP and IRG were unaffected.

Insulin secretion and insulin sensitivity defects are a common feature of mild, clinically homogeneous, recently diagnosed type II (Non-insulin-dependent) diabetics

SummaryAlteration in insulin secretion and reduced peripheral sensitivity to the hormone have been reported in type II diabetes. In this paper, a comparison is made of basal glucose production (3H-6 glucose), insulin secretion and insulin sensitivityin vivo (hyperglycemic clamp) andin vitro (binding to circulating monocytes) in 24 patients with recently diagnosed type II diabetes, matched for age and fasting glycemia and divided into non-obese (14 subjects) and moderately obese (10 subjects), and in 9 non-obese controls. The non-obese diabetics were slightly hyperinsulinemic during fasting (10.8±1.0vs 4.8±0.8 µU/ml in controls, p < 0.0005), with a significant reduction in early and late insulin secretion (14.0±1.5vs 20.8 ± 2.0 µU/ml, p<0.01 and 24.8±3.3vs 34.7±2.14 µU/ml, p<0.025). The insulin sensitivity index MCR/I was significantly reduced (2.30±0.32vs 4.14±0.40, p<0.005). Endogenous glucose production was significantly increased (107±10.2vs 84±3.7 mg/m2 per min, p<0.025) and displayed a positive correlation with fasting glycemia (r=0.51, p<0.05). Insulin binding to monocytes was significantly lower than in controls (2.36±0.22%vs 4.06±0.32%, p<0.0005). Moderately obese diabetics also were significantly hyperinsulinemic in the fasting state (18.1±2.8 µU/ml, p<0.0005vs controls) but, typically, lacked the early secretory phase (20.6±3.6 µU/mlvs baseline, n.s.). A similar increase of hepatic glucose production (107±11.2 mg/m2 per min, p<0.025vs controls, n.s.vs non-obese diabetics) and decrease of peripheral sensitivity to insulin (MCR/I=1.78±0.31, p<0.0005vs controls, n.s.vs non-obese diabetics) was found in moderately obsese diabetics, as well as a significant reduction of insulin binding to insolated monocytes (2.62±0.4% p<0.01vs controls, n.s.vs non-obese diabetics). These results confirm that common defects of both non-obese and moderately obese type II diabetics are: lack of early phase of glucose induced insulin secretion, increase in hepatic glucose production and decrease of peripheral insulin sensitivity together with reduction of insulin binding to circulating monocytes. The hypothesis of a unique defect as a cause of hyperglycemia in type II diabetes in early clinical phase is not borne out by the results of this study. Moderate obesity, even if able to reduce insulin sensitivity, seems to be less important in determining hyperglycemia.